In 2022, surgery with negative margins is still (for better or worse!) the foundation of sarcoma treatment. Yet global local recurrence (LR) rates for adult soft tissue sarcoma are between 10 and 30%. LR is a devastating complication of sarcoma surgery. Besides the use of intraoperative frozen section, which is in itself a highly inexact science, there are no reliable intraoperative tools for sarcoma margin assessment. The intraoperative assessment of sarcoma margin adequacy is based nearly entirely upon the operative surgeon's experience and is thus terrifically subjective. Here we describe how the use of indocyanine green fluorescence angiography (ICGFA) in sarcoma surgery followed an unforeseen path that started as a research tool, was developed in an animal model of metastatic osteosarcoma, and eventually became the basis of a human clinical trial at the University of Pittsburgh. We will explore the concept of "negative margins"-the guiding principle of sarcoma surgery. We will describe our study design, its ongoing evolution, our early results, and where we think we might go next.
